Physical Sciences Inc. (PSI) proposes to develop a new adaptive optics imaging approach to high- speed 3D-retinal mapping with enhanced Fourier Domain Mode-locked (FDML) swept-source technology. PSI is currently engaged in ongoing development of high performance, high resolution multimodal adaptive optics (AO) retinal imagers. Such systems resolve and quantify cone photoreceptors across the macula, image and delineate retinal layers, reveal and map microvasculature, and image deep in the choroid, These multimodal AO systems integrate scanning laser ophthalmoscopy (AOSLO) , wide-field field imaging, retinal tracking, and, to our knowledge, are the first multimodal systems to incoprporate 1-5m swept source-based Fourier domain optical coherence tomography (AO-SSOCT) suitable for use in a broad clinical population for investigating structural and functional detail. However, in the living, fixating eye, even the smallest motions are magnified relative to the small dimensions of typical AO scan (~1 to 3 deg). At present, with existing spectral domain or swept-source technology, even high-resolution AO-OCT B-scan rates approaching 300/s (~ten times video rate @ >500 A-lines per scan) remain too slow to reliably capture the local 3D structure of particular layers, whose lateral motions can be as much as few cone diameters in the inter-line interval of several milliseconds. These scans must reach a speed sufficient to adequately cross-correlate AO-OCT cone images with AOSLO cone mosaics to derive the true multimodal advantage. The recent development of Fourier domain mode-locked [FDML] swept-source laser technology by researchers at MIT has enabled the OCT A-line rate to reach 370kline/s, and beyond. Thus, the resulting accessible B-scan rates at high resolution approach a threshold (>1000/s) where motion artifacts from the human eye do not irretrievably disrupt the local cone pattern, which is the best basis for image correction, alignment and mosaic generation over clinically useful retinal areas and volumes. To achieve these capabilities, progress on both practical multimodal AO systems and FDML or equivalent swept-source technologies is needed. PSI and its subsidiary Q-Peak are well positioned to move on both fronts together. In addition, PSI is actively engaged in the development of customized Graphical Processing Unit (GPU) algorithms and systems for real time, high-speed image cube processing that can be applied to AO-OCT. PUBLIC HEALTH RELEVANCE: The advent of high speed, high resolution ocular imaging has opened new avenues of research into the understanding and treatment of eye disease and vision loss. The proposed high performance AO instrument with high speed swept source laser technology will allow powerful new adaptive optics technology to be used by greater numbers of clinicians and scientists. These researchers will, in turn, find novel and important uses for this new tool in clinical application for detecting disease and monitoring treatment.